Spatial and temporal heterogeneity of tumor immune microenvironment between primary tumor and brain metastases in NSCLC.

BACKGROUND: Brain metastasis is a common outcome in non-small cell lung cancer, and despite aggressive treatment, its clinical outcome is still frustrating. In recent years, immunotherapy has been developing rapidly, however, its therapeutic outcomes for primary lung cancer and brain metastases are not the same, suggesting that there may be differences in the immune microenvironment of primary lung cancer and brain metastases, however, we currently know little about these differences. METHODS: Seventeen paired samples of NSCLC and their brain metastases and 45 other unpaired brain metastases samples were collected for the current study. Immunohistochemical staining was performed on all samples for the following markers: immune checkpoints CTLA-4, PD-1, PD-L1, B7-H3, B7-H4, IDO1, and EphA2; tumor-infiltrating lymphocytes (TILs) CD3, CD4, CD8, and CD20; tumor-associated microglia/macrophages (TAMs) CD68 and CD163; and tumor proliferation index Ki-67. The differences in expression of these markers were compared in 17 paired samples, and the effect of the expression level of these markers on the prognosis of patients was analyzed in lung adenocarcinoma brain metastases samples. Subsequently, multiplex immunofluorescence staining was performed in a typical lung-brain paired sample based on the aforementioned results. The multiplex immunofluorescence staining results revealed the difference in tumor immune microenvironment between primary NSCLC and brain metastases. RESULTS: In 17 paired lesions, the infiltration of CTLA-4+ (P = 0.461), PD-1+ (P = 0.106), CD3+ (P = 0.045), CD4+ (P = 0.037), CD8+ (P = 0.008), and CD20+ (P = 0.029) TILs in brain metastases were significantly decreased compared with primary tumors. No statistically significant difference was observed in the CD68 (P = 0.954) and CD163 (P = 0.654) TAM infiltration between primary NSCLC and paired brain metastases. In all the brain metastases lesions, the expression of PD-L1 is related to the time interval of brain metastases in NSCLC. In addition, the Cox proportional hazards regression models showed high expression of B7-H4 (hazard ratio [HR] = 3.276, 95% confidence interval [CI] 1.335-8.041, P = 0.010) and CD68 TAM infiltration (HR = 3.775, 95% CI 1.419-10.044, P = 0.008) were independent prognosis factors for lung adenocarcinoma brain metastases patients. CONCLUSIONS: Both temporal and spatial heterogeneity is present between the primary tumor and brain metastases of NCSLC. Brain metastases lesions exhibit a more immunosuppressive tumor immune microenvironment. B7-H4 and CD68+ TAMs may have potential therapeutic value for lung adenocarcinoma brain metastases patients.

Study of the PI3K/Akt/mTOR signaling pathway in vitro and molecular docking analysis of periplocin inhibits cell cycle progression and induces apoptosis in MDA-MB-231.

Breast cancer mainly affects women and is the second leading cause of cancer-related deaths worldwide. Breast cancer affects women aged 15-59. The current study explored periplocin's anticancer activities against breast cancer MDA-MB-231 cells by down-regulating the PI3K/Akt/mTOR pathway. The MTT assay assessed control-treated and periplocin (2.5-50 µM) treated MDA-MB-231 cell viability. ROS accumulation and apoptosis levels in periplocin-treated cells were examined using DAPI, dual staining, and Annexin V-FITC/PI assays. Caspase enzymes were studied using assay kits. Flow cytometry was used to measure cell cycle distributions. Periplocin-treated cells were analyzed using RT-PCR assays and insilico analyses for the expression of PI3K/Akt/mTOR molecules. The periplocin treatment remarkably reduced the viability of the MDA-MB-231 cells, with an IC50 concentration of 7.5 µM. The fluorescent staining assays revealed a substantial increase in ROS levels and apoptotic events in the periplocin-treated cells. The flow cytometry analysis revealed that periplocin triggered apoptosis and arrested the cell cycle in G0/G1 phases. Periplocin increased the caspase-3, -8, and -9 enzyme activities. In MDA-MB-231 cells, Periplocin decreased PI3K/Akt/mTOR activity, and in silico analysis, Periplocin was inhibited by CDK8-Cyclin C interactions. Periplocin has anticancer properties against breast cancer and may be an effective therapeutic agent for treating breast cancer.

Mid-infrared quasi-parametric chirped-pulse amplification based on Sm:LGN crystals.

We numerically demonstrate highly efficient mid-infrared quasi-parametric chirped-pulse amplification (QPCPA) based on a recently developed Sm3+-doped La3Ga5.5Nb0.5O14 (Sm:LGN) crystal. At pump wavelength around 1 µm, the broadband absorption of Sm3+ on idler pulses can enable QPCPA for femtosecond signal pulses centered at 3.5 or 5 µm, with a conversion efficiency approaching the quantum limit. Due to suppression of back conversion, such mid-infrared QPCPA exhibits robustness against phase-mismatch and pump-intensity variation. The Sm:LGN-based QPCPA will provide an efficient approach for converting currently well-developed intense laser pulses at 1 µm to mid-infrared ultrashort pulses.

Sub-picosecond tunable mid-infrared light source for driving high-efficiency optical rectification.

Optical rectification (OR) is a popular way to generate coherent terahertz radiation. Here, we develop a sub-picosecond mid-infrared (mid-IR) light source with a tailored wavelength and pulse duration for enhancing the OR efficiency. Numerical simulations for a LiNbO3-based OR with tilted pulse-front excitation are first conducted to determine the optimal parameters of pump wavelength and pulse duration, demonstrating that the OR efficiency pumped by 4-µm sub-picosecond (0.5-0.6 ps) pulses is approximately twice the value with 0.8-µm pump at the same conditions. Guided by the simulation results, we build a BaGa4Se7-based optical parametric chirped-pulse amplification system with 1030-nm thin-disk pump and broadband mid-IR seeds. The output performances of >200-µJ pulse energy, ∼600-fs pulse duration and 1-kHz pulse repetition rate are achieved in a spectral range tunable from 3.5 to 5 µm. The large energy scalability and high parameter tunability make the light source attractive to high-efficiency OR in various materials.

ZDHHC15 promotes glioma malignancy and acts as a novel prognostic biomarker for patients with glioma.

BACKGROUND: Glioma is the most common and aggressive tumor in the adult brain. Recent studies have indicated that Zinc finger DHHC-type palmitoyltransferases (ZDHHCs) play vital roles in regulating the progression of glioma. ZDHHC15, a member of the ZDHHCs family, participates in various physiological activities in the brain. However, the biological functions and related mechanisms of ZDHHC15 in glioma remain poorly understood. METHODS: Data from multiple glioma-associated datasets were used to investigate the expression profiles and potential biological functions of ZDHHC15 in glioma. Expression of ZDHHC15 and its association with clinicopathological characteristics in glioma were validated by quantitative reverse transcription PCR (RT-qPCR) and immunohistochemical experiments. GO enrichment analysis, KEGG analysis, GSEA analysis, CCK-8, EdU, transwell, and western blotting assays were performed to confirm the functions and mechanism of ZDHHC15 in glioma. Moreover, we performed Kaplan-Meier analysis and Cox progression analysis to explore the prognostic significance of ZDHHC15 in glioma patients. RESULTS: ZDHHC15 expression was significantly up-regulated in glioma and positively associated with malignant phenotypes. Results from the GO and KEGG enrichment analysis revealed that ZDHHC15 was involved in regulating cell cycle and migration. Knockdown of ZDHHC15 inhibited glioma cell proliferation and migration, while overexpression of ZDHHC15 presented opposite effects on glioma cells. Besides, results from GSEA analysis suggested that ZDHHC15 was enriched in STAT3 signaling pathway. Knockdown or overexpression of ZDHHC15 indeed affected the activation of STAT3 signaling pathway. Additionally, we identified ZDHHC15 as an independent prognostic biomarker in glioma, and higher expression of ZDHHC15 predicted a poorer prognosis in glioma patients. CONCLUSION: Our findings suggest that ZDHHC15 promotes glioma malignancy and can serve as a novel prognostic biomarker for glioma patients. Targeting ZDHHC15 may be a promising therapeutic strategy for glioma.

Near-Infrared Photooxygenation Theranostics Used for the Specific Mapping and Modulating of Amyloid-ß Aggregation.

The photooxygenation of amyloid-ß (Aß) protein is considered a promising strategy against Alzheimer's disease (AD). The inhibition of Aß aggregation or depolymerization of Aß aggregates can effectively alleviate and improve the condition of AD. Herein, we report a series of "off-on" near-infrared quinolinium photosensitizers (QM20-QM22) based on D-π-A structures using a target-sensing catalyst activation (TaSCAc) strategy. They exhibit turn-on fluorescence when bonded to Aß aggregates and generate singlet oxygen to achieve the specific imaging and photooxygenation of Aß aggregates, leading to attenuated Aß aggregates, enhancing their clearance through the microglial lysosomal pathway, decreasing their neurotoxicity. This study will shed light on the development of the photooxygenation of misfolded proteins for the treatment of neurodegenerative diseases.

Repeated Neonatal Exposure to Sevoflurane Induces Age-Dependent Impairments in Cognition and Synaptic Plasticity in Mice.

BACKGROUND: Sevoflurane is a volatile anesthetic that is widely used in pediatric anesthesia due to its low toxicity. However, whether neonatal exposure to sevoflurane induces long-lasting cognitive impairment remains unclear. It has been reported that neuronal injury is the main cause of sevoflurane-induced learning and memory disabilities in the development of brain. But, the specific mechanism is not well elucidated. The injury of synapse occurs earlier than that of neuronal cell in brain injury. The synaptic plasticity is involved in learning and memory. METHODS: We compared the learning and memory ability of neonatal mice to sevoflurane for once or three times in vitro and synaptic plasticity as well as neuronal excitability in vivo. In this study, neonatal C57BL/6J mice were exposed to 3% sevoflurane for 2 h on postnatal day 7 (P7) or once daily for 3 consecutive days (P7/8/9). The Morris water maze test was performed to evaluate the cognitive performance on P31 and P61, respectively. Theta burst stimulation-induced long-term potentiation (LTP) was measured in acute hippocampal slices from P38 and P68 mice to assess the synaptic plasticity. Primary hippocampal neurons were isolated from 24-h-old mice and exposed to different doses of sevoflurane (1, 2, and 3 minimum alveolar anesthetic concentration [MAC]) for 6 h to examine the neuronal excitability. RESULTS: The results showed that compared with the control, repeated exposure to sevoflurane resulted in significant cognitive impairment in adolescent mice, while showing no effect on adult mice. Repeated exposure to sevoflurane remarkably attenuated hippocampal LTP of adolescent mice, which turned to normal in adult mice. No significant difference of LTP was observed between control mice and one-dose sevoflurane-treated mice both in adolescent and adult mice. In primary hippocampal neurons, 2 MAC and 3 MAC sevoflurane delayed neuronal excitation and dose-dependently reduced the number of evoked action potentials compared with control. These effects disappeared after a 24-h recovery. CONCLUSIONS: These data suggested that sevoflurane may impair cognitive performance and neuronal plasticity when administered repeatedly or in a high MAC during infancy, which is noticeable during adolescence but alleviates during adulthood.

Loss of Raptor induces Sertoli cells into an undifferentiated state in mice.

In mammals, testis development is triggered by the expression of the sex-determining Y-chromosome gene SRY to commit the Sertoli cell (SC) fate at gonadal sex determination in the fetus. Several genes have been identified to be required to promote the testis pathway following SRY activation (i.e., SRY box 9 (SOX9)) in an embryo; however, it largely remains unknown about the genes and the mechanisms involved in stabilizing the testis pathway after birth and throughout adulthood. Herein, we report postnatal males with SC-specific deletion of Raptor demonstrated the absence of SC unique identity and adversely acquired granulosa cell-like characteristics, along with loss of tubular architecture and scattered distribution of SCs and germ cells. Subsequent genome-wide analysis by RNA sequencing revealed a profound decrease in the transcripts of testis genes (i.e., Sox9, Sox8, and anti-Mullerian hormone (Amh)) and, conversely, an increase in ovary genes (i.e., LIM/Homeobox gene 9 (Lhx9), Forkhead box L2 (Foxl2) and Follistatin (Fst)); these changes were further confirmed by immunofluorescence and quantitative reverse-transcription polymerase chain reaction. Importantly, co-immunofluorescence demonstrated that Raptor deficiency induced SCs dedifferentiation into a progenitor state; the Raptor-mutant gonads showed some ovarian somatic cell features, accompanied by enhanced female steroidogenesis and elevated estrogen levels, yet the zona pellucida 3 (ZP3)-positive terminally feminized oocytes were not observed. In vitro experiments with primary SCs suggested that Raptor is likely involved in the fibroblast growth factor 9 (FGF9)-induced formation of cell junctions among SCs. Our results established that Raptor is required to maintain SC identity, stabilize the male pathway, and promote testis development.

Efficient generation of mid-infrared few-cycle pulses by the intrapulse difference-frequency generation in YCOB.

Yttrium calcium oxyborate (YCOB) crystals have been widely applied for generating intense near-infrared laser pulses by optical parametric amplification. Here, we show that the YCOB crystals oriented in both the XZ and XY principal planes possess broadband phase-matching property of intrapulse difference-frequency generation in the mid-infrared region. Few-cycle pulses tunable from 2 to 4 µm are experimentally produced by using a 7.5-fs pump laser at 800 nm, in which the conversion efficiency can be as high as 2.5%. With a large-size crystal and high-power pump laser, intrapulse difference-frequency generation based on YCOB may provide a new route for directly producing intense few-cycle mid-infrared pulses.

A quinoline derived D-A-D type fluorescent probe for sensing tetrameric transthyretin.

Nowadays, with an upward trend in the prevalence of intracerebral amyloidosis, it is of great significance to use fluorescent probes for early diagnosis in vitro. In this study, a quinoline-derived D-A-D type chemosensor was rationally designed and synthesized as a probe for the sensitive detection of tetrameric transthyretin (WT-TTR).

CKIP-1 augments autophagy in steatotic hepatocytes by inhibiting Akt/mTOR signal pathway.

Nonalcoholic fatty liver disease (NAFLD), which is characterized by aberrant accumulation of intrahepatic triglycerides and lipid droplets (LDs) in the liver cells, is becoming increasingly prevalent at an alarming rate worldwide. LDs can be consumed by either hydrolysis or autophagy, which is shown to be of importance in the regulation of hepatic lipid metabolism. We have shown that deficiency of pleckstrin homology domain-containing casein kinase 2 interacting protein-1 (CKIP-1), a scaffold protein that interacts with various proteins in multiple signal pathways, in mice aggravates high-fat diet induced fatty liver. However, its underlying mechanisms remain largely unknown. In this study, we found that the mRNA and protein levels of CKIP-1 decreased dramatically in steatotic HepG2 cells induced by oleic acid (OA) treatment. Coincidently, hepatic autophagy was also dynamically regulated in steatotic HepG2 cells. In addition, overexpression of CKIP-1 activated autophagy by suppression of Akt/mTOR signaling, which in turn reduced lipid accumulation. Moreover, these phenomena were reversed in CKIP-1-shRNA transfected steatotic hepatocytes. To further evaluate the potential role of CKIP-1 in autophagy, we determined the level of autophagy related proteins in CKIP-1 knockout mice. These results supported our findings in vitro. In summary, we found CKIP-1 to be a positive regulator of hepatic autophagy and a promising therapeutic target for treatment of NAFLD.

Few-cycle pulses tunable from 3 to 7 µm via intrapulse difference-frequency generation in oxide LGN crystals.

An ultrashort mid-infrared (IR) source beyond 5 µm is crucial for a plethora of existing and emerging applications in spectroscopy, medical diagnostics, and high-field physics. Nonlinear generation of such sources from well-developed near-IR lasers, however, remains a challenge due to the limitation of mid-IR crystals. Based on oxide La3Ga5.5Nb0.5O14 (LGN) crystals, here we report the generation of femtosecond pulses tunable from 3 to 7 µm by intrapulse difference-frequency generation of 7.5 fs, 800 nm pulses. The efficiency and bandwidth dependences on pump polarization and crystal length are studied for both Type-I and Type-II phase-matching configurations. Maximum pulse energy of ∼10nJ is generated at 5.2 µm with a conversion efficiency of ∼0.14%. Because of the few-cycle pump pulse duration, the generated mid-IR pulses are as short as about three cycles. These results, to the best of our knowledge, represent the first experimental demonstration of LGN in generating mid-IR ultrashort pulses.

Phosphorescent iridium(III) complex for efficient sensing of hypochlorite and imaging in living cells.

In consideration of the strong oxidizing power of hypochlorite (ClO-), which could cleave CN moiety, a cyclometalated iridium (III) complex (Ir-Ts) modified hydrazide group as the response unit was synthesized to sensitively and selectively detect ClO- under neutral condition. Upon addition of ClO-, a 21-fold emission enhancement at 574 nm was observed and phosphorescent product was formed due to the cleavage of CN moiety. The probe Ir-Ts displayed rapid response (<15 s) and high selectivity toward ClO- with a low detection limit of 86 nM. More importantly, bioimaging of ClO- was further studied in living cells.

A randomized controlled trial evaluating the hemodynamic impact of ultrasound-guided great auricular nerve block in middle ear microsurgery.

BACKGROUND: The peri-operative effectiveness of ultrasound-guided great auricular nerve block (GANB) in patients, especially in adult patients undergoing middle ear microsurgery remains unclear. We hypothesized that ultrasound-guided GANB would decrease the hemodynamic responsiveness to incision and opioid consumption in middle ear microsurgery as well as the post-operative analgesia requirement. METHODS: Sixty patients undergoing middle ear microsurgery were randomized into two equal groups to receive either a GANB with 2 ml of 0.25% ropivacaine under ultrasound guidance (GANB group) or to receive a blank control intervention (without any performed injection) before general anesthesia inductions. The primary outcomes were hemodynamic changes of MAP (mean artery pressure) and HR (heart rate) to skin incision. The secondary endpoints were to determine the consumptions of propofol and remifentanil during the operation and the incidence of remedial analgesia 48 h post-operation to maintain VAS ≤ 3. RESULTS: The MAP post incision in GANB group was significantly lower than that in control group (GANB group 93.83 ± 11.72 mmHg vs. control group 100.87 ± 12.65 mmHg, P = 0.029). The increases for MAP and HR post incision were also lower in GANB group (∆MAP GANB group 11.90 ± 8.32 mmHg vs. control group 19.83 ± 10.37 mmHg, P = 0.002; ∆HR GANB group 3.67 ± 5.30 beat min- 1 vs. control group 8.23 ± 8.56 beat min- 1, P = 0.016). Remifentanil consumption was significantly decreased in GANB group (GANB group 401.55 ± 100.51 µg h- 1 vs. control group 697.34 ± 215.45 µg h- 1, P = 0.000). The incidence of remedial analgesia post-operation in GANB group (5/30) was significantly lower than that in control group (20/30, P = 0.000). CONCLUSION: Ultrasound-guided GANB decreases the hemodynamic responsiveness to incision and remifentanil consumption in middle ear microsurgery as well as the post-operative analgesia requirement. TRIAL REGISTRATION: This trial was retrospectively registered at http://www.chictr.org.cn with the registration number of ChiCTR1800014333 on 6 January, 2018.

Intermittency, Moments, and Friction Coefficient during the Subcritical Transition of Channel Flow.

The intermittent distribution of localized turbulent structures is a key feature of the subcritical transitions in channel flows, which are studied in this paper with a wind channel and theoretical modeling. Entrance disturbances are introduced by small beads, and localized turbulent patches can be triggered at low Reynolds numbers (Re). High turbulence intensity represents strong ability of perturbation spread, and a maximum turbulence intensity is found for every test case as Re ≥ 950, where the turbulence fraction increases abruptly with Re. Skewness can reflect the velocity defects of localized turbulent patches and is revealed to become negative when Re is as low as about 660. It is shown that the third-order moments of the midplane streamwise velocities have minima, while the corresponding forth-order moments have maxima during the transition. These kinematic extremes and different variation scenarios of the friction coefficient during the transition are explained with an intermittent structure model, where the robust localized turbulent structure is simplified as a turbulence unit, a structure whose statistical properties are only weak functions of the Reynolds number.

Hepatopancreas transcriptome analysis of Chinese mitten crab (Eriocheir sinensis) with white hepatopancreas syndrome.

White hepatopancreas is a syndrome that has recently emerged in aquaculture of Chinese mitten crab (Eriocheir sinensis). High lethality of the disease caused large economic loss, which drew considerable attention of fish farmers and scientific researchers. In this study, hepatopancreas reference transcriptome was de novo assembled and differential expression analysis was conducted between white hepatopancreas and normal (yellow) hepatopancreas of E. sinensis. A total of 90,687 transcripts were assembled, and 27,387 were annotated. Transcriptomic comparison revealed 69 differentially expressed genes between individuals featuring white hepatopancreas and yellow hepatopancreas. Genes associated with immune response and cell death, include thioredoxin-related transmembrane protein 1, hemocytin, methuselah-like 1, and E3 ubiquitin-protein ligase, and they were up-regulated, whereas titin and 5-formyltetrahydrofolate cyclo-ligase, which are genes related to cell proliferation, were down-regulated in E. sinensis with white hepatopancreas syndrome. Our study provides novel insights into genetic causes of formation and novel gene markers for detection of white hepatopancreas syndrome in aquaculture of E. sinensis.

Th1-, Th2-, and Th17-associated cytokine expression in hypopharyngeal carcinoma and clinical significance.

Th0 cells differentiate into Th1 or Th2 depending on multiple transcription factors acting on specific time points to regulate gene expression. Th17 cells, a subset of IL-17-producing T cells distinct from Th1 or Th2 cells, have been described as key players in inflammation and autoimmune diseases as well as cancer development. In the present study, 53 patients with hypopharyngeal cancer were included. The expression levels of Th1-, Th2- and Th17-associated cytokines in hypopharyngeal cancer tissues and pericarcinoma tissues were detected. The relationship between Th1, Th2, or Th17 infiltration and metastasis was studied. Our results showed that the mRNA and protein expressions of Th1 cytokines were lower, while the expressions of Th2 and Th17 cytokines were higher in tumor tissues, and the intensity of expression was strengthened with clinical stage increasing. Cancer tissues had higher level expressions of Th2 and Th17 cytokines than that of pericarcinoma tissues. From the above data, we speculated that high expressions of Th2- and Th17-associated cytokines in hypopharyngeal carcinoma may contribute to cancer development and metastasis.

Nitric oxide-induced lipophagic defects contribute to testosterone deficiency in rats with spinal cord injury.

Introduction: Males with acute spinal cord injury (SCI) frequently exhibit testosterone deficiency and reproductive dysfunction. While such incidence rates are high in chronic patients, the underlying mechanisms remain elusive. Methods and results: Herein, we generated a rat SCI model, which recapitulated complications in human males, including low testosterone levels and spermatogenic disorders. Proteomics analyses showed that the differentially expressed proteins were mostly enriched in lipid metabolism and steroid metabolism and biosynthesis. In SCI rats, we observed that testicular nitric oxide (NO) levels were elevated and lipid droplet-autophagosome co-localization in testicular interstitial cells was decreased. We hypothesized that NO impaired lipophagy in Leydig cells (LCs) to disrupt testosterone biosynthesis and spermatogenesis. As postulated, exogenous NO donor (S-nitroso-N-acetylpenicillamine (SNAP)) treatment markedly raised NO levels and disturbed lipophagy via the AMPK/mTOR/ULK1 pathway, and ultimately impaired testosterone production in mouse LCs. However, such alterations were not fully observed when cells were treated with an endogenous NO donor (L-arginine), suggesting that mouse LCs were devoid of an endogenous NO-production system. Alternatively, activated (M1) macrophages were predominant NO sources, as inducible NO synthase inhibition attenuated lipophagic defects and testosterone insufficiency in LCs in a macrophage-LC co-culture system. In scavenging NO (2-4-carboxyphenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (CPTIO)) we effectively restored lipophagy and testosterone levels both in vitro and in vivo, and importantly, spermatogenesis in vivo. Autophagy activation by LYN-1604 also promoted lipid degradation and testosterone synthesis. Discussion: In summary, we showed that NO-disrupted-lipophagy caused testosterone deficiency following SCI, and NO clearance or autophagy activation could be effective in preventing reproductive dysfunction in males with SCI.

Prognostic value and chemotherapy response prediction of a proliferation essential gene signature in colon cancer.

BACKGROUND: Colon cancer is a common malignant tumor in the digestive tract. Exploring new treatment targets is of great significance for improving the survival rate of colon cancer patients. The present study mainly analyzes the impact of proliferation essential genes (PLEGs) on the prognosis and chemotherapy response of colon cancer patients, as well as identifying the expression and cellular functions of important PLEG. METHODS: The DepMap database was utilized for identification of PLEG in colon cancer cells. Through DEGs screening, WGCNA, univariate cox regression survival analysis, and LASSO, a PLEG signature (PLEGs) model was constructed. The impact of PLEGs on the prognosis of colon cancer patients and their response to chemotherapy was further analyzed. Finally, we conducted a random forest analysis and implemented functional experiments to investigate the prominent PLEG that is linked to the development of colon cancer. RESULTS: Based on the expression and prognosis of PLEG, we constructed a PLEGs prognosis model which can effectively predict the prognosis of colon cancer patients and their response to chemotherapy treatment. Random forest analysis showed that UBA1 is a key PLEG in the progression of colon cancer. Immunohistochemistry results revealed that UBA1 protein is significantly upregulated in colon cancer tissues. Cell functional experiments demonstrated that knocking down UBA1 can inhibit the proliferation, invasion, and migration abilities of colon cancer cells. CONCLUSION: PLEGs have the potential to serve as predictive biomarkers for prognosis and chemotherapy response in colon cancer patients. Among the PLEG, UBA1 plays a prominent role in promoting the malignant progression of colon cancer cells.

Guillain-Barré Syndrome with Incomplete Oculomotor Nerve Palsy after Traumatic Brain Injury: Case Report and Literature Review.

Guillain-Barré syndrome (GBS) is a severe peripheral neuroinflammatory demyelinating disease characterized by symmetrical progressive limb weakness, which can be accompanied by cranial nerve and sensory disturbances. There is usually a history of bacterial or viral infection prior to onset. GBS is rarely seen after traumatic brain injury (TBI). We report a case of a 66-year-old male patient who presented with dilated pupils, followed by respiratory failure and symmetrical quadriplegia during a conservative treatment for TBI. He was eventually diagnosed with GBS and was treated with intravenous immunoglobulin, followed by rehabilitation therapy with a good recovery. We summarize previous similar cases and analyze possible causes. It is suggested that the possibility of GBS should be considered when unexplained symptoms occurred in patients with TBI, such as respiratory failure, dilated pupils, and limb weakness.